Incidence, Severity, and Treatment of Bevacizumab and Ramucirumab Induced Hypertension in Patients with Non-Squamous, Non-Small Cell Lung Cancer

Bevacizumab and ramucirumab are vascular endothelial growth factor (VEGF) inhibitors which are used in combination with traditional platinum-based chemotherapies as treatment for non-squamous, non-small cell lung cancer (NSCLC). These therapies are associated with hypertension; but incidence and severity are not well defined outside of clinical trials and there are no clear recommendations for treatment of this adverse effect. In this single healthcare system retrospective study, data was collected from 41 patients treated with bevacizumab or ramucirumab for non-squamous, NSCLC at UNC Medical Center from April 4, 2014 to May 31, 2020. Blood pressure and antihypertensive medication data was abstracted from oncology visit medical notes at baseline and every 4 weeks for 24 weeks following initiation of VEGF-inhibitor treatment. Following initiation of bevacizumab or ramucirumab, the frequency of patients with ACC/AHA Stage 1 hypertension (SBP 130-139 or DBP 80-89) increased from 24.4% at baseline to 31.7% at week 8; and ACC/AHA Stage 2 hypertension (SBP > 140 or DBP > 90) increased from 31.7% at baseline to 39.0% at week 8. By week 4, 14 (34.2%) patients developed all grade CTCAE (grade >1) hypertension which increased to 18 (43.9%) at week 8. Overall, 5 (12.2%) patients developed CTCAE high grade (grade 3 or 4) hypertension at week 4. Only four total patients were initiated on antihypertensive medications to treat this adverse effect, with ACE inhibitors (n=3) being the most frequently prescribed. Additionally, only two patients with pre-existing hypertension had increases to their antihypertensive regimens both at week 4. These results illustrate the high frequency and severity of VEGF-inhibitor induced hypertension and suggest a potential under treatment of this adverse effect. Our study highlights the need for future studies to further investigate the real-world incidence and severity of bevacizumab and ramucirumab induced hypertension and prescribing trends for this adverse effect.